title: Simvastatin attenuates radiation-induced tissue damage in mice.
abstract: The aim of this study was to investigate the protective effect of simvastatin against radiation-induced tissue injury in mice. Mice were radiated with 4 Gy or 8 Gy after 20 mg/kg/d simvastatin treatment over 2 weeks. Morphological changes were observed in the jejunum and bone marrow, and apoptotic cells were determined in both tissues. Peripheral blood cells were counted, and the superoxide dismutase (SOD) activity and the malondialdehyde (MDA) level in tissues of both thymus and spleen were measured. Compared with the radiation-only group, 20 mg/kg/d simvastatin administration significantly increased the mean villi height and decreased apoptotic cells in jejunum tissue, and stimulated regeneration and reduced apoptotic cells in bone marrow. Peripheral blood cell analysis revealed that simvastatin treatment induced a larger number of red blood cells and increased the hemoglobin level present after 4 Gy of radiation. Interestingly, it was also found that the number of peripheral endothelial progenitor cells was markedly increased following simvastatin administration. Antioxidant determination for tissues displayed that simvastatin therapy increased the SOD activity after both 4 and 8 Gy of radiation, but only decreased the MDA level after 4 Gy. Simvastatin ameliorated radiation-induced tissue damage in mice. The radioprotective effect of simvastatin was possibly related to inhibition of apoptosis and improvement of oxygen-carrying and antioxidant activities.
authors.affiliation: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, 415 Feng-Yang Road, Shanghai 200003, China.
authors.forename: Xinbin
authors.initials: X
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Guojun
authors.initials: G
authors.lastname: Jiang
authors.forename: Min
authors.initials: M
authors.lastname: Ni
authors.forename: Yaping
authors.initials: Y
authors.lastname: Deng
authors.forename: Jian
authors.initials: J
authors.lastname: Cai
authors.forename: Zhangpeng
authors.initials: Z
authors.lastname: Li
authors.forename: Fuming
authors.initials: F
authors.lastname: Shen
authors.forename: Xia
authors.initials: X
authors.lastname: Tao
mesh_terms: D054508:Acute Radiation Syndrome / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019821:Simvastatin / Q000008:administration & dosage* / Q000009:adverse effects; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D019821:Simvastatin
keywords: endothelial progenitor cells; radiation; radioprotection; simvastatin; tissue damage